The purpose of the proposed experiments is to determine the influence of cerebral norepinephrine on cerebral cortical oxidative metabolism and local vascular responses to energy demand, and the physiological mechanism underlying this influence. The model chosen for these studies is the unilateral chemical lesion of the nucleus locus ceruleus in rats and cats. This lesion results in an ipsilateral depletion of cortical norepinephrine. Local cerebral cortical oxidative metabolism and vascular responsivity will be monitored in-situ by non-invasive optical techniques. These techniques continuously measure changes in the redox state of cytochrome oxidase, hemoglobin saturation and relative blood volume by dual wavelength reflection spectrophotometry and mitochondrial NADH by microfluorometry. Microelectrodes will be used to concomitantly measure the electrocortical activity, tissue oxygen content, and extracellular potassium activity. Since, in the normal awake animal, locus ceruleus neurons fire at higher rates during conditions of stress, these studies will explore the response of the local blood volume and the mitochondrial respiratory chain during steady state, and dynamically activated, metabolic demand. Heightened metabolic demand will be induced by direct cortical electrical stimulation and by administration of amphetamine. The mechanism underlying the influence of norepinephrine on cerebral physiology will be investigated vis-a-vis the appearance of denervation supersensitivity of beta adrenergic receptors in whole brain and isolated brain capillaries.